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PURPOSE OF REVIEW: The identification of regulatory T cells (Tregs) as regulators of immunological self-tolerance has stimulated tremendous interest in the field. Over the past 12 months, new studies have added greatly to our understanding of the role of Tregs in autoimmune disease, details of which are presented here. RECENT FINDINGS: In this review, the mechanism of action of Tregs, their antigen specificity and their frequency and function in different autoimmune diseases is explored. Currently available data on the role of transforming growth factor-beta, the reciprocal relationship between Tregs and Th17 cells, Treg markers, and current therapeutic approaches are evaluated. Other regulatory cells, which have been recently identified to play a significant role in autoimmunity, are described. SUMMARY: Increasing insights into understanding the complex mechanisms of action of Tregs have already led to exciting therapeutic advances. This review provides an in-depth analysis of recent advances in the field of Tregs in autoimmunity. It highlights targets for future immunomodulatory therapy that may treat and potentially cure autoimmune disease, and it identifies areas for future research.